Ontology highlight
ABSTRACT: Background
M? muscarinic acetylcholine receptor (M?-mAChR) is stably expressed in the myocardium, but its pathophysiological role remains largely undefined. This study aimed to investigate the role of M?-mAChR in cardiac hypertrophy induced by angiotensin II (Ang II) and elucidate the underlying mechanisms.Methods
Cardiac-specific M?-mAChR overexpression transgenic (TG) mice and rat H9c2 cardiomyoblasts with ectopic expression of M?-mAChR were established. Models of cardiac hypertrophy were induced by transverse aortic constriction (TAC) or Ang II infusion in the mice in vivo, and by isoproterenol (ISO) or Ang II treatment of H9c2 cells in vitro. Cardiac hypertrophy was evaluated by electrocardiography (ECG) measurement, hemodynamic measurement and histological analysis. mRNA and protein expression were detected by real-time RT-PCR and Western blot analysis.Results
M?-mAChR was upregulated in hypertrophic heart, while M?-mAChR expression did not change significantly. M?-mAChR overexpression significantly attenuated the increased expression of atrial natriuretic peptide and ?-myosin heavy chain induced by Ang II both in vivo and in vitro. In addition, M?-mAChR overexpression downregulated AT1 receptor expression and inhibited the activation of MAPK signaling in the heart.Conclusion
The upregulation of M?-mAChR during myocardial hypertrophy could relieve the hypertrophic response provoked by Ang II, and the mechanism may involve the inhibition of MAPK signaling through the downregulation of AT1 receptor.
SUBMITTER: Liu Y
PROVIDER: S-EPMC3819674 | biostudies-literature | 2013 Sep
REPOSITORIES: biostudies-literature
Liu Yan Y Wang Shu S Wang Chao C Song Haoxin H Han Hongmei H Hang Pengzhou P Jiang Yanan Y Wei Lanlan L Huo Rong R Sun Lihua L Gao Xu X Lu Yanjie Y Du Zhimin Z
Journal of translational medicine 20130912
<h4>Background</h4>M₃ muscarinic acetylcholine receptor (M₃-mAChR) is stably expressed in the myocardium, but its pathophysiological role remains largely undefined. This study aimed to investigate the role of M₃-mAChR in cardiac hypertrophy induced by angiotensin II (Ang II) and elucidate the underlying mechanisms.<h4>Methods</h4>Cardiac-specific M₃-mAChR overexpression transgenic (TG) mice and rat H9c2 cardiomyoblasts with ectopic expression of M₃-mAChR were established. Models of cardiac hyper ...[more]